The current surgical management of invasive cervical cancer includes radical hysterectomy with pelvic lymphadenectomy. The lymphadenectomy is considered therapeutic and is aimed at removing lymph-node-bearing tissue surrounding the iliac vessels and superficial obturator fossa. Extending the external iliac lymphadenectomy to the femoral canal can be difficult, with exposure decreasing as the area is approached. The external iliac vessels, with their branches and tributaries, and the genitofemoral nerve potentially are in harm's way, and the region is rich in lymphatic vessels (potentially increasing the risk of lymphocyst or lymphedema). Some experts have suggested that the distal limit of dissection need not extend beyond the deep circumflex iliac vein.1,2 The present study was done to determine the appropriateness of this landmark.
Materials and Methods
We studied all women undergoing primary radical hysterectomy with pelvic lymphadenectomy for cervical cancer from June 1995 through September 1998. The operations were done by the author and a gynecologic oncology fellow. Surgery was not abandoned for grossly positive lymph nodes.
For pelvic lymphadenectomy, the entire length of the external and common iliac vessels and the attachments of the lymph-node-bearing tissue to the psoas muscle were divided and the genitofemoral nerve was dissected free. The external and common iliac vessels with the lymphatic tissue were separated from the psoas muscle. The lymph node bundle was freed from the dorsolateral to the ventral side of the external iliac vein, then left in place. The bundle was freed from the external iliac artery completely and left attached to the partially dissected external iliac vein bundle. The bundle was then separated from the common iliac lymph nodes and dissected off the internal iliac artery and off the ventral and medial aspects of the external iliac vein to the obturator fossa. The bundle was then separated from the dorsal aspect (underside) of the external iliac vein and from the obturator nerve in an attempt to include all lymph-node-bearing tissue in the obturator fossa superficial to the nerve. Care was taken to ligate or coagulate the lymphatics connected to the bundle in the caudal aspect of the fossa. A thorough common iliac lymphadenectomy and, in selected cases, a para-aortic lymphadenectomy was also performed.
During dissection of the distal (caudal), anterior (ventral) aspect of the external iliac vessels, a careful search was made for the deep circumflex iliac vein. One or more lymph nodes immediately cephalad to this vein were excised and sent as adjacent external iliac lymph nodes. Any lymph nodes between the vein and the femoral canal were excised and sent as distal external iliac lymph nodes. The distance from the vein to the canal was measured bilaterally. The remainder of the lymph nodes were sent en bloc as pelvic lymph nodes or separately as external iliac and obturator lymph nodes.
The appropriately labeled lymph nodes were received in the laboratory either fresh or formalin-fixed. Lymph nodes were identified by careful palpation by the attending pathologist (SG) and by serial sectioning through the fibroadipose tissue. Smaller nodes were sampled entirely. Larger nodes were bisected and a representative sample was submitted. Usually at least half of the node was included, with attention to any firm white areas. After proper fixation, the tissue was processed as usual. Sections of 3–5μm were stained with hematoxylin and eosin and examined by light microscopy. Special stains and immunohistochemistry were performed if necessary.
During accrual, data were collected on patient characteristics, operative and pathologic findings, and subsequent outcomes. Statistical analysis included χ2 as a test of association, t test, Mann-Whitney rank-sum test, Pearson correlation coefficient, and multivariate logistic regression. P < .05 was considered statistically significant. Data were analyzed by SPSS software (SPSS, Inc, Chicago, IL).
Seventy-one women were entered during the 40-month study and none were excluded. The mean age was 42 years (range 22–77). Fourteen (19%) were obese (body mass index exceeding 30 kg/m2). Fifty-three (74%) were International Federation of Gynecology and Obstetrics stage IB1 (IA2 = 5; IB2 = 10; IIA = 3). Fifty-five (77%) had squamous cell carcinoma, 15 had adenocarcinoma (all IB1), and one had adenosquamous carcinoma. Twenty-one (29%) were diagnosed by cone biopsy, with a mean interval to operation of 32 days (range 7–42).
The mean maximum cervical diameter and tumor depth (dividing the cervix into thirds) are given in Table 1. Twenty-five (35%) of the tumors involved lymph-vascular spaces. Microscopic tumor foci were found in the parametrial tissues in five women (7%).
The median number of pelvic lymph nodes removed per patient was 24 (range nine to 68), with 23 patients (32%) having fewer than 20 nodes removed. The deep circumflex iliac vein was not found on either side in eight women and was not found on the right side in two. In four subjects, the distances from the vein to the femoral canal on the right and left sides were slightly different (less than 5 mm difference). Using the symmetrical measurement in 57 subjects, the single measurement in two, and the average in four, the mean distance from the deep circumflex iliac vein to the femoral canal in the 63 subjects was 16 mm (range 5–30). The numbers of lymph nodes removed adjacent and distal to the deep circumflex iliac vein are given in Table 2. In some cases, the most distal external iliac lymph nodes overlaid the deep circumflex iliac vein and both were sent as a combined group. There was no significant correlation between the number of right (r = .384) or left (r = .185) distal nodes removed and the distance from the vein. There was no significant difference in the number of distal nodes removed (right or left) whether the distance from the vein to the canal was less than or greater than 15 mm. There was also no significant correlation between the number of distal nodes removed and age (Pearson correlation coefficient) or obesity (unpaired t test).
Although the procedures were not timed, we estimate that bilateral dissection of the distal external iliac lymph nodes added approximately 10 minutes to the operative time. Complications potentially attributable to removal of the distal nodes are given in Table 3. Injury of the veins and nerves occurred during this portion of the dissection. Lymphocyst and lymphedema were included because of the concentration of lymphatic vessels in this region.
Lymph node metastases were found in 13 patients (18%) (Figure 1). Six had a single pelvic lymph node metastasis (microscopic only in two subjects), five had unilateral involvement of two pelvic lymph nodes (one woman also had a microscopically positive para-aortic lymph node), and two subjects had bilateral macroscopic pelvic lymph node metastases (one woman had two macroscopically positive para-aortic lymph nodes). The subject with para-aortic lymph node metastases had a single left distal external iliac lymph node that was macroscopically positive. The specimen taken just above this (adjacent) contained fat only, and the right distal (two) and adjacent (one) nodes were negative. Another subject (one of two women with one microscopically positive lymph node) had a single microscopic lymph node metastasis in one of two right adjacent lymph nodes, and no lymph nodes were found distal to this.
On univariate analysis, significant factors for node positivity were severity of stage (P = .016), depth of invasion (P = .001), larger size of the cervix (P = .010), lymph-vascular space involvement (P = .0013), and parametrial tumor foci (P = .012). There was no significant difference in the number of women with positive nodes with different histologic types. When the above factors were included in a multivariate stepwise logistic regression analysis, the only one found to have an independent effect on prediction of node positivity was lymph-vascular space involvement (estimated relative risk 7.7; 95% confidence interval 1.2, 47.9).
Follow-up information was obtained for the 61 women treated before June 1, 1998. Thirteen (21%) received postoperative adjuvant radiotherapy for positive lymph nodes (ten subjects), positive parametria (one subject), or full-thickness invasion (two subjects). Three patients were lost to follow-up at 1, 12, and 14 months (all without evidence of recurrence). Three developed isolated local recurrences at 3, 5, and 10 months, but remained without evidence of further recurrence at 35, 19, and 35 months, respectively. Four other subjects developed recurrence (one locoregional, one regional, and two distant) at 7–19 months and subsequently died of disease at 8–30 months. The mean length of follow-up for the 56 women who were disease-free at last follow-up (excluding the woman lost to follow-up at 1 month) was 20 months (range 2–37). Significantly more patients had recurrence with deeper invasion and with lymph-vascular space involvement. There was no significant difference in recurrence by stage (P = .056), cervical diameter (P = .057), parametrial involvement (P = .344), or histologic type (P = .779). No factors were found to have an independent effect on recurrence.
Dating back to the report by Taussig3 in 1934 (pelvic lymphadenectomy with radiation therapy for cervical cancer) and the report by Meigs4 in 1944 (combined radical hysterectomy and pelvic lymphadenectomy for early-stage cervical cancer), pelvic lymphadenectomy has become an integral part of the surgical treatment of early invasive cervical cancer. Recent careful studies have confirmed the superficial obturator and external iliac lymph nodes as the most common sites of pelvic lymph node metastasis in early cervical cancer.5,6 The adjacent and distal external iliac lymph nodes examined in this study are essentially the same as the “retrocrural external gland” discussed by Nelson et al7 the “suprainguinal” nodes described by Onda et al,8 and “Jackson's node” discussed by Morrow and Curtin.2 Minor controversies continue regarding the anatomic limits of dissection and the number of lymph nodes that should be removed by lymphadenectomy.1,2,5,6,9–16
One recent study of ovarian cancer demonstrated that the suprainguinal (the lowest external iliac) lymph nodes contained metastasis in 40% of node-positive women. The present study showed that external iliac lymph nodes are commonly found distal to the deep circumflex iliac vein and that the likelihood of metastases to these lymph nodes is low in women with early-stage cervical cancer. A larger number of women with lymph node metastases would be needed to clarify the risk. This study was not intended to apply to women with more advanced cervical cancer. The goal of operation is different for this group, and these tumors may have broader avenues of spread to the retroperitoneal lymph nodes.
In a patient with extensive lymph node metastases, one would suspect that the risk of metastases to the distal lymph nodes would be higher. This was the case for the one woman in the present study who had a distal lymph node metastasis. Especially in the presence of suspicious or grossly positive pelvic lymph nodes, we suggest palpation of the area with removal of suspect lymph nodes. The potential benefits are lymph node debulking,17 marking of disease sites that otherwise might be outside the radiation field,18 and better future definition of the risk of metastases at this site. We believe that involvement of distal nodes places the patient at higher risk for inguinal lymph node metastases. The results of this study suggest that in the absence of suspicious or positive lymph nodes, the deep circumflex iliac vein is an appropriate landmark for the distal limit of external iliac lymphadenectomy. A small number of lymph nodes were found distal to this vein in most women, and 8% of node-positive women had involvement of this nodal group.
1. Hatch KD. Cervical cancer. In: Berek JS, Hacker NF, eds. Practical gynecologic oncology. 2nd ed. Baltimore: Williams & Wilkins, 1994:243–83.
2. Morrow CP, Curtin JP. Gynecologic cancer surgery. New York: Churchill Livingstone, 1996:451–568.
3. Taussig FJ. Iliac lymphadenectomy with irradiation in the treatment of cancer of the cervix. Am J Obstet Gynecol 1934;98:650–67.
4. Meigs JV. Carcinoma of the cervix—the Wertheim operation. Surg Gynecol Obstet 1944;78:195–9.
5. Benedetti-Panici P, Maneschi F, Scambia G, Greggi S, Cutillo G, D'Andrea G, et al. Lymphatic spread of cervical cancer: An anatomical and pathological study based on 225 radical hysterectomies with systematic pelvic and aortic lymphadenectomy. Gynecol Oncol 1996;62:19–24.
6. Michel G, Morice P, Castaigne D, Leblanc M, Rey A, Duvillard P. Lymphatic spread in Stage Ib and II cervical carcinoma: Anatomy and surgical implications. Obstet Gynecol 1998;91:360–3.
7. Nelson JH Jr, Masterson JG, Herman PG, Benninghoff DL. Anatomy of the female pelvic and paraaortic lymphatic systems demonstrated by lymphangiography. Am J Obstet Gynecol 1964;88:460–9.
8. Onda T, Yoshikawa H, Yokota H, Yasugi T, Taketani Y. Assessment of metastasis to aortic and pelvic lymph nodes in epithelial ovarian carcinoma: A proposal for essential sites for lymph node biopsy. Cancer 1996;78:803–8.
9. Girardi F, Pickel H, Winter R. Pelvic and parametrial lymph nodes in the quality control of the surgical treatment of cervical cancer. Gynecol Oncol 1993;50:330–3.
10. Lee RA. Atlas of gynecologic surgery. Philadelphia: WB Saunders, 1992:183–6.
11. Gallup DG, Talledo OE. Surgical atlas of gynecologic oncology. Philadelphia: WB Saunders, 1994:57–8.
12. Wheeless CR Jr. Atlas of pelvic surgery. 3rd ed. Baltimore: Williams & Wilkins, 1997:424.
13. Nelson JH. Atlas of radical pelvic surgery. New York: Appleton-Century-Crofts, 1969:102.
14. van Nagell JR Jr, DePriest PD, Higgins RV, Powell DE. Surgical therapy for cervical cancer. In: Gershenson DM, DeCherney AH, Curry SL, eds. Operative gynecology. Philadelphia: WB Saunders, 1993:271–96.
15. Shingleton HM, Gusberg SB. Radical hysterectomy. In: Gusberg SB, Shingleton HM, Deppe G, eds. Female genital cancer. New York: Churchill Livingstone, 1988:535–53.
16. Shingleton HM, Thompson JD. Cancer of the cervix. In: Rock JA, Thompson JD, eds. Te Linde's operative gynecology. 8th ed. Philadelphia: Lippincott-Raven, 1997:1413–99.
17. Cosin JA, Fowler JM, Chen MD, Paley PJ, Carson LF, Twiggs LB. Pretreatment surgical staging of patients with cervical carcinoma: The case for lymph node debulking. Cancer 1998;82:2241–8.
18. Greer BE, Koh WJ, Figge DC, Russell AH, Cain JH, Tamimi HK. Gynecologic radiotherapy fields defined by intraoperative measurements. Gynecol Oncol 1990;38:421–4.